DR. FIROZ A HAKKIMMD RESPIRATORY MEDICINE

BRONCHODILATORS

SYMPATHOMIMETICS

NON- SELECTIVE

EPINEPHRINE (ADRENALINE)

EPHEDRINE

ISOPRENALINE

ORCIPRENALINE

SYMPATHOMIMETICS

β2 - SELECTIVE

SALBUTAMOL

TERBUTALINE

BAMBUTEROL

FENOTEROL

REPROTEROL

PIRBUTEROL

SALMETEROL

EFORMOTEROL

METHYLXANTHINES THEOPHYLLINE

AMINOPHYLLINE

CHOLINE THEOPHYLLINATE

HYDROXYETHYL

THEOPHYLLINE

THEOPHYLLINE ETHANOLATE

OF PIPERAZINE

ANTICHOLINERGICS ATROPINE METHONITRATE

IPRATROPIUM BROMIDE

TIOTROPIUM BROMIDE

BRONCHODILATORS

• In use for thousand of years

• Ephedra equisetina- used in ancient china

• Modern sympathomimetics

Are derivatives or analogues

Based on structure of

Epinephrine (adrenaline)

SYMPATHOMIMETICS

They are both alpha and beta adrenergic agonist that acts as a neurotransmitter in the sympathetic nervous system,

Alpha receptor being predominantly stimulatory (vasoconstriction) and beta receptor predominantly inhibitory ( relaxation of smooth muscle in the respiratory tract, vasculature and uterus)

SYMPATHOMIMETICS

β adrenergic receptors

β2 receptors produce bronchodilatation

As well as vasodilatation

β1 receptor stimulate heart muscle

• Are non selective or poorly selective and are more likely to produce unwanted effects ( tachycardia, cardiac stimulation)

• Adrenaline – alpha + beta 1 + beta 2 agonist

• Ephedrine – alpha + beta 1 + beta 2 action

• Isoprenaline – beta 1 + beta 2 agonist

Non selective sympathomimetics

• The beta agonist produce bronchodilatationby stimulating beta 2 receptors situated in the smooth muscle of the bronchial tree, from the trachea down to the terminal bronchioles. This activates the enzyme adenyl cyclase , facilitating the conversion of ATP to cyclic AMP and resulting in the relaxation of smooth muscles in the bronchial wall. It also involves the activation of protein kinase with a reduction in ionic calcium concentration in bronchial smooth muscle

Mechanism of action

•Other beneficial non bronchodilator effects include enhanced mucociliarytransport, diminished release of histamine and other chemical mediators of asthma from mast cells, inhibition of cholinergic neurotransmission and a possible increased ventilatory response to hypercapnia and hypoxia

Administration

inhalation

Oral

medication

Parenteral

medication

• Preferred route is inhalation from MDI

• 10 % of fraction leaving device reaches lungs, remaining impacting in oropharynx and being swallowed

• Systemic side effects are generally insignificant in comparison to oral administration

• Rapid onset of action compared with same drug taken orally

• Onset of 3-6 min, 80% bronchodilatation in 5 min. Reaching peak in 30- 60 min, effect wearing off over 3-6 hr.

Inhalation

• If unable to manage inhaled therapy

• Slow onset of action , produce bronchodilatation after about 30 min and reaching a peak at 1-2 hr

Oral medication

• In severe exacerbations

• Onset of action is rapid, occuring within a few minutes and peak effect reached sooner than inhalation , duration of action being 4 hrs

Parenteral medication

• When swallowed may undergo conjugation in gut wall as well as in liver

• Relatively small quantities of these drugs are excreted unchanged by the kidneys and dosage modification is unnecessary in renal insufficiency

• Slightly penetrate the blood brain barrier and also cross placenta so that oral medication is perhaps better avoided in pregnancy.

Metabolism and excretion

• Principal dose limiting adverse effect of beta agonist is Skeletal muscle tremors, particularly affecting hands.

• Muscle cramps, tachycardia ( reduced peripheral vascular resistance, vasodilatation occuring as a result of stimulation of receptors in vascular smooth muscle)

• Metabolic effects like hypokalemia, brought about by stimulation of pancreatic beta 2 receptors , resulting in increased insulin release and an intracellular potassium shift

• Non specific effects – dryness of mouth, nausea , vomiting

Adverse effects

• Paradoxical bronchoconstriction occuring after patients have taken beta 2 agonist by pressurized MDI or nebulization, are unusual and may be by drug or the constituent of propellant or physical charecteristics like temperature , ph , osmolality.

• May worsen ventilation – perfusion mismatch in short term.may arise if pulmonary vessels that were previously reflexly constricted in response to local hypoxia are dilated by beta 2 receptor stimulation so that blood is shunted into areas of lung still relatively poorly ventilated. This can be overcome by administration of oxygen as a routine.

Drug oral dose Iv bolus Iv infusion MDI Neb

solution

salbutamol 4mg tds 250µg 5µg /min

initialy

then 3 –

20µg/ min

100-200 µg 2.5- 5 mg

terbutaline 5mg bd 250- 500

µg

1.5- 5 µg/

min

250- 500

µg

5-10 mg

salmeterol 25-50µg

formoterol 12- 24µg

Dosage

• To relieve wheeze

• To prevent or reduce wheeze in patients with exercise induced asthma

• Long acting bronchodilators may also be useful as a single dose before bedtime for patients who continue to experience nocturnal wheeze despite otherwise optimal treatment

• Adrenaline ( epinephrine ) given to patients developing bronchospasm, serious upper airway narrowing, hypotension with collapse ( bee or wasp sting) (dose 3-5 ml of 1 : 10000 iv)

Use in respiratory medicine